The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration

椎间盘营养在椎间盘退变的病因学和临床治疗中的作用

• 批准号: 10531879
• 负责人: SARAH E GULLBRAND
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531879
• 关键词: Adult; Affect; Animal Model; Animals; Area; Articular Range of Motion; Atomic Force Microscopy; Back Pain; Biochemistry; Biological Assay; Biology; Blood Vessels; Bone Density; Cadaver; Caregivers; Caring; Cartilage; Cells; Clinical; Clinical Research; Clinical Treatment; Convection; Custom; Devices; Diffusion; Economic Burden; Etiology; Euthanasia; Faculty; Fibrocartilages; Funding; Gene Expression Profiling; General Population; Goals; Health; Heart; Histology; Homeostasis; Human; Image; Incidence; Intervertebral disc structure; K-Series Research Career Programs; Knowledge; Link; Location; Low Back Pain; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Mechanics; Mentors; Microfils; Military Personnel; Modeling; Motion; Needles; Nutrient; Nutritional; Oryctolagus cuniculus; Outcome; Pain; Pathway interactions; Patient-Focused Outcomes; Patients; Physical therapy; Play; Positioning Attribute; Prevalence; Property; Puncture procedure; Questionnaires; Regimen; Research; Research Activity; Research Personnel; Role; Sampling; Severities; Source; Spectroscopy, Fourier Transform Infrared; Spinal; Stroke; Structure; Time; Tissue Engineering; Training; Transport Process; Travel; United States; Vertebral column; Veterans; Visual; Waste Products; Weight-Bearing state; Work; active duty; analog; bone; career development; chronic pain; contrast enhanced; density; disability; disc regeneration; distraction; efficacious treatment; experience; fluid flow; functional outcomes; improved; in vivo; indexing; intervertebral disk degeneration; mechanical load; mechanical properties; mineralization; nucleus pulposus; nutrition; pain relief; patient response; predictive tools; regenerative; response; skills; small molecule; social; spine bone structure; success; treatment strategy; vertebra body; wasting

Low back pain, most commonly caused by degeneration of the intervertebral disc, places a significant social and economic burden on the general public, active duty military and veterans alike. The intervertebral discs of the spine are the largest avascular structures in the body, and the cells within the disc therefore rely on the transport of nutrients and waste products across the vertebral endplate to maintain disc homeostasis. A compromise in transport across the vertebral endplate interface is therefore implicated in the initiation and progression of disc degeneration. The overarching goal of this proposal is twofold: (1) Elucidate the properties of the boney and cartilage endplates that affect trans-endplate transport and how alterations in transport contribute to disc degeneration, and (2) investigate alterations to trans-endplate transport and disc health during non-operative treatment of patients with back pain and their correlation with pain relief and functional outcomes. These goals will be accomplished via the following specific aims: Aim 1: Determine the structural, mechanical and compositional properties of the vertebral endplates affecting diffusion and convection into healthy and degenerative human intervertebral discs. A custom MRI-compatible device will be constructed to quantify the transport properties of cadaveric human endplate samples under both diffusion and convection (fluid flow). Transport properties will then be correlated with boney endplate compositional and local mechanical properties, as assayed via µCT, histology, Fourier transform infrared spectroscopy (FTIR), local strain tracking analysis, and atomic force microscopy (AFM). Aim 2: Establish correlations between intervertebral disc degeneration, trans-endplate small molecule diffusion, and vertebral endplate structure, composition and mechanics in an in vivo rabbit model. Intervertebral disc degeneration will be induced in vivo in a rabbit model via puncture of the disc with a 16G or 21G needle. Animals will be euthanized at 4, 8, and 16 weeks post-puncture to generate a spectrum of degeneration from mild (21G puncture) to severe (16G puncture). Small molecule trans-endplate diffusion into the disc will be quantified via post-contrast enhanced MRI T1-mapping. The boney and cartilage endplates will be assayed via microFil enhanced µCT to determine bone and vascular density. Composition and mechanics of the endplates will be assayed via FTIR and AFM, respectively. Degeneration of the intervertebral disc will be assessed via MRI T2-mapping, histology, biochemistry and gene expression assays. Aim 3: Determine the feasibility and preliminary outcomes of quantifying the effect of physical therapy on trans-endplate diffusion into the degenerative disc in patients with back pain. Human patients with back pain concomitant with disc degeneration will be subjected to MRI T2- mapping and post-contrast enhanced T1-mapping at time points prior to and 6 weeks after physical therapy. Standard questionnaires of pain (visual analog scale), function (Oswestry Disability Index), as well as objective measures of lumbar range of motion, will be completed at the same time points to establish correlations between disc health, nutrition and patient outcomes.

腰痛，最常见的是椎间盘变性引起的， 将重要的社会和经济伯恩恩放在公众现役 军人和退伍军人。脊柱的椎间盘是最大的血管 因此，体内的结构以及光盘中的细胞依赖于运输 椎骨端板上的营养和废品以维护椎间盘 稳态。跨椎骨接口的运输妥协是 因此，在光盘退化的主动性和进展中实施。这 该提议的总体目标是双重的：（1）阐明骨骼的特性 影响运输的软骨终结物以及运输方式的变化 有助于椎间盘变性，（2）研究对跨式板的变化 在腰痛患者的非手术治疗期间运输和椎间盘健康 它们与缓解疼痛和功能结果的相关性。这些目标将是 通过以下特定目标完成：目标1：确定结构， 影响扩散的椎骨终结物的机械和复合特性 并将对话成健康，退化性的人类椎间盘。习俗 将构建与MRI兼容的设备，以量化 在扩散和运输下（流体流）下的尸体人类终板样品。 然后，运输属性将与Boney Endplate复合材料和本地相关 机械性能，通过µCT，组织学，傅立叶变换红外分配 光谱（FTIR），局部应变跟踪分析和原子力显微镜（AFM）。 AIM 2：建立椎间盘变性之间的相关性 小分子扩散以及椎骨终板结构，组成和力学 体内兔模型。椎间盘变性将在兔子的体内诱导 通过用16G或21克针的盘穿穿刺模型。动物将在 诉讼后4、8和16周，从中部产生变性 （21g穿刺）至重度（16G穿刺）。小分子的反式板扩散到 将通过对比后增强的MRI T1映射来量化光盘。笨蛋和 软骨终板将通过缩微纤维增强的µCT分配，以确定骨骼和 血管密度。终结的组成和力学将通过FTIR分配 和AFM。椎间盘的变性将通过MRI评估 T2映射，组织学，生物化学和基因表达分析。目标3：确定 量化物理疗法对的可行性和初步结果 背痛患者的转换板扩散到退化性椎间盘中。人类 与椎间盘变性同时进行背痛的患者将接受MRI T2- 在时间点和6周之前的映射和对比后增强了T1映射 物理治疗后。疼痛的标准问卷（视觉模拟量表），功能 （Oswestry残疾指数），以及腰运动范围的客观测量， 将在同一时间完成以建立光盘健康之间的相关性， 营养和患者预后。